1-74738724-C-G

Variant names:

• chr1-74738724-C-G
• NM_138467.3:c.290C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138467.3(TYW3):​c.290C>G​(p.Thr97Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TYW3 NM_138467.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25

Genes affected

TYW3 (HGNC:24757): (tRNA-yW synthesizing protein 3 homolog) Wybutosine (yW) is a hypermodified guanosine at the 3-prime position adjacent to the anticodon of phenylalanine tRNA that stabilizes codon-anticodon interactions during decoding on the ribosome. TYW3 is the human homolog of a yeast gene essential for yW synthesis (Noma and Suzuki, 2006).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09570372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYW3	NM_138467.3	c.290C>G	p.Thr97Ser	missense_variant	Exon 3 of 6	ENST00000370867.8	NP_612476.1
TYW3	XM_006710347.3	c.290C>G	p.Thr97Ser	missense_variant	Exon 3 of 7		XP_006710410.1
TYW3	NM_001162916.2	c.255+2102C>G		intron_variant	Intron 2 of 4		NP_001156388.1
TYW3	NR_027962.2	n.496C>G		non_coding_transcript_exon_variant	Exon 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYW3	ENST00000370867.8	c.290C>G	p.Thr97Ser	missense_variant	Exon 3 of 6	1	NM_138467.3	ENSP00000359904.3
TYW3	ENST00000479111	c.-71C>G		5_prime_UTR_variant	Exon 4 of 7	3		ENSP00000477469.1
TYW3	ENST00000483990	c.-71C>G		5_prime_UTR_variant	Exon 2 of 4	3		ENSP00000476365.1
TYW3	ENST00000457880.6	c.255+2102C>G		intron_variant	Intron 2 of 4	2		ENSP00000407025.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.290C>G (p.T97S) alteration is located in exon 3 (coding exon 3) of the TYW3 gene. This alteration results from a C to G substitution at nucleotide position 290, causing the threonine (T) at amino acid position 97 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.78
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.17	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.068
Sift	Benign	0.17	T
Sift4G	Benign	0.81	T
Polyphen		0.019	B
Vest4		0.092
MutPred		0.50		Gain of disorder (P = 0.0795);
MVP		0.081
MPC		0.084
ClinPred		0.41	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.042
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-75204408;